Promiscuity comes at a price: catalytic versatility vs efficiency in different metal ion derivatives of the potential bioremediator GpdQ

Daumann, Lena J., McCarthy, Bianca Y., Hadler, Kieran S., Murray, Tracy P., Gahan, Lawrence R., Larrabee, James A., Ollis, David L. and Schenk, Gerhard (2013) Promiscuity comes at a price: catalytic versatility vs efficiency in different metal ion derivatives of the potential bioremediator GpdQ. Biochimica Et Biophysica Acta-Proteins and Proteomics, 1834 1: 425-432. doi:10.1016/j.bbapap.2012.02.004


Author Daumann, Lena J.
McCarthy, Bianca Y.
Hadler, Kieran S.
Murray, Tracy P.
Gahan, Lawrence R.
Larrabee, James A.
Ollis, David L.
Schenk, Gerhard
Title Promiscuity comes at a price: catalytic versatility vs efficiency in different metal ion derivatives of the potential bioremediator GpdQ
Formatted title
Promiscuity comes at a price: catalytic versatility vs efficiency in different metal ion derivatives of the potential bioremediator GpdQ
Journal name Biochimica Et Biophysica Acta-Proteins and Proteomics   Check publisher's open access policy
ISSN 1570-9639
Publication date 2013-01
Sub-type Article (original research)
DOI 10.1016/j.bbapap.2012.02.004
Volume 1834
Issue 1
Start page 425
End page 432
Total pages 8
Place of publication Netherlands
Publisher Elsevier
Collection year 2014
Language eng
Formatted abstract
The glycerophosphodiesterase from Enterobacter aerogenes (GpdQ) is a highly promiscuous dinuclear metallohydrolase with respect to both substrate specificity and metal ion composition. While this promiscuity may adversely affect the enzyme's catalytic efficiency its ability to hydrolyse some organophosphates (OPs) and by-products of OP degradation have turned GpdQ into a promising candidate for bioremedial applications. Here, we investigated both metal ion binding and the effect of the metal ion composition on catalysis. The prevalent in vivo metal ion composition for GpdQ is proposed to be of the type Fe(II)Zn(II), a reflection of natural abundance rather than catalytic optimisation. The Fe(II) appears to have lower binding affinity than other divalent metal ions, and the catalytic efficiency of this mixed metal center is considerably smaller than that of Mn(II), Co(II) or Cd(II)-containing derivatives of GpdQ. Interestingly, metal ion replacements do not only affect catalytic efficiency but also the optimal pH range for the reaction, suggesting that different metal ion combinations may employ different mechanistic strategies. These metal ion-triggered modulations are likely to be mediated via an extensive hydrogen bond network that links the two metal ion binding sites via residues in the substrate binding pocket. The observed functional diversity may be the cause for the modest catalytic efficiency of wild-type GpdQ but may also be essential to enable the enzyme to evolve rapidly to alter substrate specificity and enhance kcat values, as has recently been demonstrated in a directed evolution experiment. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.

Highlights ► GpdQ is a highly promiscuous phosphoesterase and is useful as a bioremediator. ► The metal ion composition modulates the reaction mechanism. ► The catalytic efficiency of GpdQ is modest. ► Modest catalytic efficiency may be the basis for rapid functional adaptability.
Keyword Binuclear metallohydrolases
Bioremediation
Glycerophosphodiesterase
Metal ion replacement
Reaction mechanism
Enterobacter-aerogenes
Active-site
Degrading enzyme
Glycerophosphodiesterase
Uteroferrin
Biomimetics
Flexibility
Reactivity
Mechanism
Binding
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 14 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 08 Mar 2013, 11:08:06 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences